Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers.
Jarvis, James A
Cremades Casasin, Nunilo
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Fusco, G., Chen, S. W., Williamson, P. T., Cascella, R., Perni, M., Jarvis, J. A., Cecchi, C., et al. (2017). Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers.. Science, 358 (6369)https://doi.org/10.1126/science.aan6160
Oligomeric species populated during the aggregation process of α-synuclein have been linked to neuronal impairment in Parkinson's disease and related neurodegenerative disorders. By using solution and solid-state nuclear magnetic resonance techniques in conjunction with other structural methods, we identified the fundamental characteristics that enable toxic α-synuclein oligomers to perturb biological membranes and disrupt cellular function; these include a highly lipophilic element that promotes strong membrane interactions and a structured region that inserts into lipid bilayers and disrupts their integrity. In support of these conclusions, mutations that target the region that promotes strong membrane interactions by α-synuclein oligomers suppressed their toxicity in neuroblastoma cells and primary cortical neurons.
External DOI: https://doi.org/10.1126/science.aan6160
This record's URL: https://www.repository.cam.ac.uk/handle/1810/296718
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